It’s taken a week to untangle, but the Astrazeneca plc and Oxford University phase III trial of their adenovirus-based coronavirus vaccine is back up and running in the U.K.
As that trial resumes, Pfizer Inc. and Biontech SE submitted an amended protocol to the FDA for upping their phase III COVID-19 vaccine trial from 30,000 to as many as 44,000 participants, allowing for enrollment of new populations. The new demographics include patients as young as 16 plus those with chronic, stable HIV, and hepatitis C or B infections. Additional safety and efficacy data are also on the amendment.
Pfizer-Biontech received $1.95 billion in July from the U.S. government for the first 100 million doses of their jointly developed mRNA-based COVID-19 vaccine by October, with an implied price per dose of $19.50. The agreement includes the government’s option to buy as many as 500 million additional doses. The companies said they could potentially manufacture more than 1.3 billion doses by the end of 2021.
Details on an illness that prompted the Astrazeneca-Oxford halt are being held close to the vest by investigators. Astrazeneca and Oxford, the trial sponsor, said they cannot disclose what they termed “further medical information.”
The university said much the same: “We cannot disclose medical information about the illness for reasons of participant confidentiality.” Oxford added that in large trials such as this “it is expected that some participants will become unwell and every case must be carefully evaluated to ensure careful assessment of safety.”
The study of AZD-1222 resumed with the blessing of the U.K.’s Medicines Health Regulatory Authority on Sept. 12 after a Sept. 6 standard review process prompted the voluntary halt. During the pause, independent committees and international regulators pored over the safety data, concluded the trial was safe and passed their findings to the regulatory authority.
The trial investigators and the participants will be updated with “relevant information” to be disclosed on global clinical registries according to trial and regulatory standards, Astrazeneca noted.
While few specifics at the heart of the pause have been revealed, a participant information sheet for a phase II/III study of the vaccine, sometimes called ChAdOx1-nCov-19, noted at least one adverse event. The sheet, with a version date of July 12, noted that while neither allergic reactions nor Guillain-Barré syndrome had been seen in the study, “one volunteer in the trials of ChAdOx1 nCoV-19 developed symptoms of transverse myelitis (inflammation in the spinal cord), which has not required medical treatment and is being investigated, though the cause is uncertain.”
AZD-122 uses a replication-deficient chimpanzee viral vector that’s based on a weakened version of an adenovirus that causes infections in chimps and contains SARS-CoV-2 virus spike protein’s genetic material.
In late July, Cambridge, U.K.-based Astrazeneca posted interim data from AZD-1222’s phase I/II blinded, multicenter, randomized, controlled clinical trial of 1,077 healthy adults showing the vaccine was tolerated and generated a robust immune response against the virus. The data showed a fourfold increase in antibodies to the virus spike protein in 95% of the patients a month after injection. A T-cell response, peaking by day 14, was also induced and maintained for two months afterward.
BioWorld’s tracking of the global race for the vaccine, as of Sept. 1, details 725 therapeutics and vaccines, as well as 435 diagnostics, for the SARS-CoV-2 virus that causes COVID-19. The U.S. government, through its Operation Warp Speed effort, continues to forecast availability of a vaccine by the end of 2020 or early 2021, promising that the speed will not circumvent safety.
As of the end of August, only two therapeutics hold emergency use authorization (EUA) in the U.S. for treating the disease: remdesivir (Veklury, Gilead Sciences Inc.) and convalescent plasma. A third EUA, granted to hydroxychloroquine in March, was revoked three months later following data that showed no benefit.